Esomeprazole with clopidogrel reduces peptic ulcer recurrence, compared with clopidogrel alone, in patients with atherosclerosis

Gastroenterology. 2011 Mar;140(3):791-8. doi: 10.1053/j.gastro.2010.11.056. Epub 2010 Dec 7.

Abstract

Background & aims: We performed a prospective, randomized, controlled study to compare the combination of esomeprazole and clopidogrel vs clopidogrel alone in preventing recurrent peptic ulcers in patients with atherosclerosis and a history of peptic ulcers. We also investigated the effects of esomeprazole on the antiplatelet action of clopidogrel.

Methods: From January 2008 to January 2010, long-term clopidogrel users with histories of peptic ulcers who did not have peptic ulcers at an initial endoscopy examination were assigned randomly to receive the combination of esomeprazole (20 mg/day, before breakfast) and clopidogrel (75 mg/day, at bedtime), or clopidogrel alone for 6 months. A follow-up endoscopy examination was performed at the end of the sixth month and whenever severe symptoms occurred. Platelet aggregation tests were performed on days 1 and 28 for 42 consecutive patients who participated in the pharmacodynamic study.

Results: The cumulative incidence of recurrent peptic ulcer during the 6-month period was 1.2% among patients given the combination of esomeprazole and clopidogrel (n = 83) and 11.0% among patients given clopidogrel alone (n = 82) (difference, 9.8%; 95% confidence interval, 2.6%-17.0%; P = .009). In the group given the combination therapy, there were no differences in the percentages of aggregated platelets on days 1 and 28 (31.0% ± 20.5% vs 30.1% ± 16.5%).

Conclusions: Among patients with atherosclerosis and a history of peptic ulcers, the combination of esomeprazole and clopidogrel reduced recurrence of peptic ulcers, compared with clopidogrel alone. Esomeprazole does not influence the action of clopidogrel on platelet aggregation.

Trial registration: ClinicalTrials.gov NCT01138969.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Atherosclerosis / blood
  • Atherosclerosis / complications
  • Atherosclerosis / drug therapy*
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Drug Interactions
  • Endoscopy, Gastrointestinal
  • Esomeprazole / adverse effects
  • Esomeprazole / therapeutic use*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Peptic Ulcer / complications
  • Peptic Ulcer / drug therapy*
  • Peptic Ulcer / pathology
  • Peptic Ulcer / prevention & control
  • Phenotype
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Prospective Studies
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use*
  • Risk Assessment
  • Secondary Prevention
  • Taiwan
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Esomeprazole
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT01138969